Brison has served as the Liberal Party's Finance Critic since September 2010. He is also a member of the Trilateral Commission and has been named by the World Economic Forum (WEF) of Davos, Switzerland, as one of its "Young Global Leaders."

In July 2000, Brison resigned his seat so that PC leader Joe Clark could enter the House of Commons. In the interim, Brison was appointed co-chair of the Tories' Election Policy Platform Committee, and became vice-president of investment banking at Yorkton Securities in Toronto.

When the 2000 election was called in October, Clark stood for election in a Calgary, Alberta riding. Brison returned as the PC candidate in Kings—Hants, and was returned to Parliament.[3] In 2001, he served as the party's Finance and Industry critic, and was vice-chairman of the House of Commons Finance committee. Brison came out as gay in 2002, saying that he is "not a gay politician, but a politician who happens to be gay." He became the fourth sitting Member of Parliament to do so after Svend Robinson, Réal Ménard and Libby Davies. As well, he was the first openly gay MP to sit as a member of the Progressive Conservative Party.

In 2003, following Clark's retirement, Brison ran for the leadership of the Progressive Conservatives[5] on a platform of "new ideas", that consisted of Employment Insurance reform, more private involvement in health care, integrated defense strategy with the US, and socially liberal policies. At the leadership convention, his campaign was dealt a crucial blow by John Herron who defected to the MacKay camp. Despite gaining votes on the second ballot, Brison was eliminated by a mere three votes and threw his support to Jim Prentice. Prentice lost on the final ballot to MacKay (who won with the support of David Orchard). He fought publicly with other members of his party, particularly Elsie Wayne, over their opposition to same-sex marriage.

On December 10, 2003, four days after Brison voted in favour of the PCs merging with the Canadian Alliance to form the new Conservative Party of Canada, Brison announced that he would cross the floor and sit as a Liberal MP.[6] He stated that he had reservations about the perceived dominance of former members of the more socially conservative Canadian Alliance in the new party. Brison was criticized for this move, however, especially because he had actively supported the merger when it was first proposed. Others had also pointed out that as Finance Critic, he had been outspoken in his attacks on Paul Martin who was Finance Minister; Brison was criticized as an opportunist for switching parties and accepting a position as parliamentary secretary. Brison claimed his enthusiasm for the merger had become discernibly lukewarm in the final weeks before the vote. He indicated that he would honour his prior commitment to support the proposal, but said that he would reconsider his allegiance once the results were announced.

On December 12, he was appointed as a parliamentary secretary to the Prime Minister with special emphasis on Canada-U.S. Relations and sworn into the Queen's Privy Council for Canada. In the 2004 election, Brison was re-elected, his first victory as a Liberal. On July 20, 2004, Brison was named to cabinet as Minister of Public Works in Martin's post-election shuffle.[7] In doing so, he became Canada's first openly gay cabinet minister.[8]

As the youngest member of cabinet, Brison also served on three cabinet committees – Treasury Board, Domestic Affairs, and Expenditure Review. Previously, he had served as Vice-Chairman of the Standing Committee on Finance, been a member of the Standing Committee on Industry, the Standing Committee on Foreign Affairs and International Trade, and the Standing Committee on Government Operations and Estimates.

He is also a member of the Canada-U.S. Inter-Parliamentary Group and has served as the vice-president of the Canadian group of the Inter-Parliamentary Union where he took part in conferences in Moscow and New York. He was also part of the Canadian delegation sent to two annual meetings of the European Bank for Reconstruction and Development in London.

On April 22, 2006, Brison entered the race for the leadership of the Liberal Party of Canada. His Liberal leadership platform emphasised both environmentalism and economic reform calling for a "green" platform that called for personal and corporate tax cuts to prompt business growth and curb pollution.[9] Brison won 4.0% of the vote on the first ballot with 192 delegates, leaving him in 6th place out of eight candidates. He dropped out and threw his support behind Bob Rae. When Bob Rae dropped out on the third ballot and released his delegates, Scott Brison opted to support the politically similar Michael Ignatieff. The final winner of the leadership convention was Stéphane Dion.